Could “trained immunity” be induced by live attenuated vaccines protect against COVID-19? Review of available evidence

Abstract

Coronavirus disease 2019 (COVID-19) represents a severe global public health threat. Caused by SARS-Cov-2, COVID-19 is characterized by high transmission rate that correlates with high viral load. The full clinical spectrum of the illness, the prevalence rates of mild symptomatic and asymptomatic cases, and the case fatality rates are still poorly understood, highlighting the importance of early preventive measures. Unfortunately, appropriate vaccination against SARS-Cov-2 is not yet available. Unless a target vaccine is developed, COVID-19 impacts will be devastating. “Trained immunity” (TI), which could be induced by live attenuated vaccines (LAVs), is a potential public health preventive approach to boost the host immune system. Trained innate immune cells demonstrated phenotypical and functional changes leading them to acquire immunological memory and amplify their responses against subsequent infections. This phenomenon could have important public health preventive implications by harnessing the early immune responses against COVID-19, restricting its progression, and suppressing its infectivity. Some LAVs have induced a broad, nonspecific, protection against unrelated pathogens and decreased mortality from conditions other than the targeted infectious diseases. This review summarizes the relevant literature and 1) emphasizes the role of available LAVs as potential stimulants for TI and 2) proposes this phenomenon as a potential preventive approach against COVID-19 that needs thoughtful consideration and further investigation. Clinical trials in this field are then urgently needed in line of vaccine and treatment unavailability. This is specifically true when considering two evolving scenarios; the virus spread may not diminish with warm weather, and that it will erupt a second-hit severe outbreak next winter.